Viscosity measuring apparatus and method of use

ABSTRACT

A blood viscosity measuring system and method that monitors the rising head of a column of fluid representing a living being&#39;s blood in-vivo to determine the blood viscosity over a range of shears. The system includes a capillary tube, at least a portion of which is located within the vascular system of the being, and a riser tube, having a liquid therein coupled to the capillary tube. A sensor and associated microprocessor are provided to determine the change in the height of the liquid in the riser tube at plural points along the length of the tube from which the viscosity is calculated.

RELATED APPLICATIONS

[0001] This application is a Continuation application of Co-Pendingapplication Ser. No. 09/631,046, filed Aug. 1, 2000, which in turn is aContinuation application of application Ser. No. 09/383,177 filed onAug. 25, 1999 (now U.S. Pat. No. 6,261,244) which in turn is aContinuation application of application Ser. No. 08/919,906 (now U.S.Pat. No. 6,019,735), all of which are entitled VISCOSITY MEASURINGAPPARATUS AND METHOD OF USE, all of which are assigned to the sameAssignee as the present invention and all of whose entire disclosuresare incorporated by reference herein.

BACKGROUND OF THE INVENTION

[0002] This invention relates generally to an apparatus and method formeasuring the viscosity of liquids, and more particularly, an apparatusand methods for measuring the viscosity of the blood of a living beingin-vivo and over a wide range of shears.

[0003] The importance of determining the viscosity of blood iswell-known. Fibrogen, Viscosity and White Blood Cell Count Are MajorRisk Factors for Ischemic Heart Disease, by Yarnell et al., Circulation,Vol. 83, No. 3, March 1991; Postprandial Changes in Plasma and SerumViscosity and Plasma Lipids and Lipoproteins After an Acute Test Meal,by Tangney, et al., American Journal for Clinical Nutrition,65:36-40,1997; Studies of Plasma Viscosity in PrimaryHyperlipoproteinaemia, by Leonhardt et al., Atherosclerosis 28,29-40,1977; Effects of Lipoproteins on Plasma Viscosity, by Seplowitz, et al.,Atherosclerosis 38, 89-95, 1981; Hyperviscosity Syndrome in aHypercholesterolemic Patient with Primary Biliary Cirrhosis, Rosenson,et al., Gastroenterology, Vol. 98, No. 5, 1990; Blood Viscosity and Riskof Cardiovascular Events:the Edinburgh Artery Study, by Lowe et al.,British Journal of Hematology, 96, 168-171, 1997; Blood RheologyAssociated with Cardiovascular Risk Factors and Chronic CardiovascularDiseases: Results of an Epidemiologic Cross-Sectional Study, by Koenig,et al., Angiology, The Journal of Vascular Diseases, November 1988;Importance of Blood Viscoelasticity in Arteriosclerosis, by Hell, etal., Angiology, The Journal of Vascular Diseases, June, 1989; ThermalMethod for Continuous Blood-Velocity Measurements in Large BloodVessels, and Cardiac-Output Determination, by Delanois, Medical andBiological Engineering, Vol. 11, No. 2, March 1973; Fluid Mechanics inAtherosclerosis, by Nerem, et al., Handbook of Bioengineering, Chapter21, 1985.

[0004] Much effort has been made to develop apparatus and methods fordetermining the viscosity of blood. Theory and Design of DisposableClinical Blood Viscometer, by Litt et al., Biorheology, 25, 697-712,1988; Automated Measurement of Plasma Viscosity by Capillary Viscometer,by Cooke, et al., Journal of Clinical Pathology 41,1213-1216,1988; ANovel Computerized Viscometer/Rheometer by Jimenez and Kostic, Rev.Scientific Instruments 65, Vol 1, January 1994; A New Instrument for theMeasurement of Plasma-Viscosity, by John Harkness, The Lancet, pp.280-281, Aug. 10, 1963; Blood Viscosity and Raynaud's Disease, byPringle, et al., The Lancet, pp. 1086-1089, May 22, 1965; Measurement ofBlood Viscosity Using a Conicylindrical Viscometer, by Walker et al.,Medical and Biological Engineering, pp. 551-557, September 1976.

[0005] In addition, there are a number of patents relating to bloodviscosity measuring apparatus and methods. See for example, U.S. Pat.Nos. 3,342,063 (Smythe et al.); 3,720,097 (Kron); 3,999,538 (Philpot,Jr.); 4,083,363 (Philpot); 4,149,405 (Ringrose); 4,165,632 (Weber, et.al.); 4,517,830 (Gunn, deceased, et. al.); 4,519,239 (Kiesewetter, et.al.); 4,554,821 (Kiesewetter, et. al.); 4,858,127 (Kron, et. al.);4,884,577 (Merrill); 4,947,678 (Hori et al.); 5,181,415 (Esvan et al.);5,257,529 (Taniguchi et al.); 5,271,398 (Schlain et al.); and 5,447,440(Davis, et. al.).

[0006] The Smythe '063 patent discloses an apparatus for measuring theviscosity of a blood sample based on the pressure detected in a conduitcontaining the blood sample. The Kron '097 patent discloses a method andapparatus for determining the blood viscosity using a flowmeter, apressure source and a pressure transducer. The Philpot '538 patentdiscloses a method of determining blood viscosity by withdrawing bloodfrom the vein at a constant pressure for a predetermined time period andfrom the volume of blood withdrawn. The Philpot '363 patent discloses anapparatus for determining blood viscosity using a hollow needle, a meansfor withdrawing and collecting blood from the vein via the hollowneedle, a negative pressure measuring device and a timing device. TheRingrose '405 patent discloses a method for measuring the viscosity ofblood by placing a sample of it on a support and directing a beam oflight through the sample and then detecting the reflected light whilevibrating the support at a given frequency and amplitude. The Weber '632patent discloses a method and apparatus for determining the fluidity ofblood by drawing the blood through a capillary tube measuring cell intoa reservoir and then returning the blood back through the tube at aconstant flow velocity and with the pressure difference between the endsof the capillary tube being directly related to the blood viscosity. TheGunn '830 patent discloses an apparatus for determining blood viscositythat utilizes a transparent hollow tube, a needle at one end, a plungerat the other end for creating a vacuum to extract a predetermined amountand an apertured weight member that is movable within the tube and ismovable by gravity at a rate that is a function of the viscosity of theblood. The Kiesewetter '239 patent discloses an apparatus fordetermining the flow shear stress of suspensions, principally blood,using a measuring chamber comprised of a passage configuration thatsimulates the natural microcirculation of capillary passages in a being.The Kiesewetter '821 patent discloses another apparatus for determiningthe viscosity of fluids, particularly blood, that includes the use oftwo parallel branches of a flow loop in combination with a flow ratemeasuring device for measuring the flow in one of the branches fordetermining the blood viscosity. The Kron '127 patent discloses anapparatus and method for determining blood viscosity of a blood sampleover a wide range of shear rates. The Merrill '577 patent discloses anapparatus and method for determining the blood viscosity of a bloodsample using a hollow column in fluid communication with a chambercontaining a porous bed and means for measuring the blood flow ratewithin the column. The Hori '678 patent discloses a method formeasurement of the viscosity change in blood by disposing a temperaturesensor in the blood flow and stimulating the blood so as to cause aviscosity change. The Esvan '415 patent discloses an apparatus thatdetects the change in viscosity of a blood sample based on the relativeslip of a drive element and a driven element, which holds the bloodsample, that are rotated. The Taniguchi '529 patent discloses a methodand apparatus for determining the viscosity of liquids, e.g., a bloodsample, utilizing a pair of vertically-aligned tubes coupled togethervia fine tubes while using a pressure sensor to measure the change of aninternal tube pressure with the passage of time and the change of flowrate of the blood. The Bedingham '328 patent discloses an intravascularblood parameter sensing system that uses a catheter and probe having aplurality of sensors (e.g., an O₂ sensor, CO₂ sensor, etc.) formeasuring particular blood parameters in vivo. The Schlain '398 patentdiscloses a intra-vessel method and apparatus for detecting undesirablewall effect on blood parameter sensors and for moving such sensors toreduce or eliminate the wall effect. The Davis '440 patent discloses anapparatus for conducting a variety of assays that are responsive to achange in the viscosity of a sample fluid, e.g., blood.

[0007] Viscosity measuring devices and methods for fluids in general arewell-known. See for example, U.S. Pat. Nos. 1,810,992 (Dallwitz-Wegner);2,343,061 (Irany); 2,696,734 (Brunstrum et al.); 2,700,891 (Shafer);2,934,944 (Eolkin); 3,071,961 (Heigl et al.); 3,116,630 (Piros);3,137,161 (Lewis et al.); 3,138,950 (Welty et al.); 3,277,694 (Cannon etal.); 3,286,511 (Harkness); 3,435,665 (Tzentis); 3,520,179 (Reed);3,604,247 (Gramain et al.); 3,666,999 (Moreland, Jr. et al.); 3,680,362(Geerdes et al.); 3,699,804 (Gassmann et al.); 3,713,328 (Aritomi);3,782,173 (Van Vessem et al.); 3,864,962 (Stark et al.); 3,908,441(Virloget); 3,952,577 (Hayes et al.); 3,990,295 (Renovanz et al.);4,149,405 (Ringrose); 4,302,965 (Johnson et al.); 4,426,878 (Price etal.); 4,432,761 (Dawe); 4,616,503 (Plungis et al.); 4,637,250 (Irvine,Jr. et al.); 4,680,957 (Dodd); 4,680,958 (Ruelle et al.); 4,750,351(Ball); 4,856,322 (Langrick et al.); 4,899,575 (Chu et al.); 5,142,899(Park et al.); 5,222,497 (Ono); 5,224,375 (You et al.); 5,257,529(Taniguchi et al.); 5,327,778 (Park); and 5,365,776 (Lehmann et al.).

[0008] The following U.S. patents disclose viscosity or flow measuringdevices, or liquid level detecting devices using optical monitoring:U.S. Pat. Nos. 3,908,441 (Virloget); 5,099,698 (Kath, et. al.);5,333,497 (Br nd Dag A. et al.). The Virloget '441 patent discloses adevice for use in viscometer that detects the level of a liquid in atransparent tube using photodetection. The Kath '698 patent discloses anapparatus for optically scanning a rotameter flow gauge and determiningthe position of a float therein. The Br nd Dag A. '497 patent disclosesa method and apparatus for continuous measurement of liquid flowvelocity of two risers by a charge coupled device (CCD) sensor.

[0009] U.S. Pat. No. 5,421,328 (Bedingham) discloses an intravascularblood parameter sensing system.

[0010] A statutory invention registration, H93 (Matta et al.) disclosesan apparatus and method for measuring elongational viscosity of a testfluid using a movie or video camera to monitor a drop of the fluid undertest.

[0011] The following publications discuss red blood cell deformabilityand/or devices used for determining such: Measurement of Human Red BloodCell Deformability Using a Single Micropore on a Thin Si ₃ N ₁ Film, byOgura et al, IEEE Transactions on Biomedical Engineering, Vol. 38, No.8, August 1991; the Pall BPF4 High Efficiency Leukocyte Removal BloodProcessing Filter System, Pall Biomedical Products Corporation, 1993.

[0012] Notwithstanding the existence of the foregoing technology, a needremains for an apparatus and method for obtaining the viscosity of theblood of a living being in-vivo and over a range of shears and for theprovision of such data in a short time span.

OBJECTS OF THE INVENTION

[0013] Accordingly, it is the general object of the instant invention toprovide an apparatus and methods for meeting that need.

[0014] It is a further object of this invention to provide viscositymeasuring an apparatus and methods for determining the viscosity ofvarious fluids, e.g., blood over a range of shears.

[0015] It is still yet a further object of this invention to provide anapparatus and methods for determining viscosity of a fluid, e.g., theblood of a living being in-vivo without the need to directly measurepressure, flow and volume.

[0016] It is yet another object of this invention to provide theviscosity of the blood of a living being in a short span of time.

[0017] It is yet another object of this invention to provide anapparatus and methods for measuring the viscosity of the blood of aliving being in-vivo and with minimum invasiveness.

[0018] It is still yet another object of the present invention toprovide an apparatus and methods for measuring the viscosity of theblood of a living being that does not require the use ofanti-coagulants, or other chemicals or biologically active materials.

[0019] It is still yet another object of the present invention toprovide an apparatus and methods measuring the blood viscosity of aliving being in-vivo that comprises disposable portions for maintaininga sterile environment, ease of use and repeat testing.

[0020] It is still yet another object of the present invention toprovide a blood viscosity measuring apparatus and methods fordetermining the thixotropic point of the blood.

[0021] It is still even a further object of the present invention toprovide a viscosity measuring apparatus and method that can be used todetermine the viscosity of other materials.

[0022] It is still a further object of this invention to provide anapparatus and methods for determining the effect of vibratory energy onblood viscosity of a living being.

[0023] It is still a further object of this invention to provideapparatus and methods for applying vibratory energy to the body of aliving being to affect a beneficial change in the person's bloodviscosity.

SUMMARY OF THE INVENTION

[0024] These and other objects of this invention are achieved byproviding apparatus and methods for effecting the in-vivo measurement ofthe viscosity of the blood (or of blood plasma) of a living being, orfor effecting the measurement of the viscosity of other non-newtonianfluids, cosmetics, oil, grease, etc, at plural shear rates.

[0025] In accordance with one aspect of the invention the apparatuscomprises blood sampling means and calculation means. The blood samplingmeans, e.g., a capillary tube of predetermined internal diameter andpredetermined length, at least a portion of which is arranged to belocated in the body of the being, e.g., placed intravenously, forexposure to the being's blood, e.g., for blood to flow therethrough. Thecalculation means, e.g., a riser tube having a column of liquid therein,an associated CCD sensor, and microprocessor, is coupled to the bloodsampling means. The calculation means is arranged to determine theviscosity of the being's blood at plural shear rates.

[0026] For example, in one exemplary aspect of the invention theapparatus is used to determine the being's blood viscosity byselectively positioning the blood sampling means, e.g., the capillarytube, with respect to the calculation means, e.g., the riser tube, andselectively coupling the flow of blood therebetween, e.g., selectivelyenabling blood to flow through the capillary tube and coupling that flowto the liquid column in the riser tube, to cause that column of fluid tochange in height under the influence of gravity. The calculation means,e.g., the CCD sensor and associated microprocessor, monitors thechanging height of the column of fluid at plural points along at least aportion of the length of the riser tube and calculates the viscosity ofthe blood in accordance with a predetermined algorithm.

[0027] In accordance with another aspect of this invention vibratoryenergy, e.g., energy which is adjustable in amplitude and/or frequency,is applied to a portion of the body of the being before and/or duringthe determination of the being's blood viscosity to provide informationregarding the effect of such vibratory energy on the blood's viscosity.This information can be used to provide therapy vibratory energy to bebeing's body to alter the being's blood viscosity in the interests ofimproving blood circulation.

DESCRIPTION OF THE DRAWINGS

[0028] Other objects and many of the intended advantages of thisinvention will be readily appreciated when the same becomes betterunderstood by reference to the following detailed description whenconsidered in connection with the accompanying drawings wherein:

[0029]FIGS. 1A and 1B form an illustration and functional diagram of oneembodiment of a system for in-vivo measuring the viscosity of the bloodof a human being;

[0030]FIG. 2A is an isometric view of a portion of the system shown inFIG. 1, namely, a portion of blood receiving means and monitoring means;

[0031]FIG. 2B is an isometric view of another portion of the systemshown in FIG. 1, namely, an exemplary test station;

[0032]FIG. 3 is an illustration of the construction and function of theblood receiving means;

[0033]FIG. 4 is a graph of a parameter measured by the system if FIG. 1,namely, the “head” of the column of fluid plotted versus time;

[0034] FIGS. 5A-5G are illustrations of a portion of the system shown inFIG. 1 showing the operational sequence thereof;

[0035]FIG. 6 is an enlarged isometric view of a portion of the system,namely, a capillary tube;

[0036]FIG. 7 is a view similar to FIG. 6, but showing an alternativeembodiment of the capillary tube;

[0037]FIG. 8A is a view similar to FIGS. 6 and 7, but showing analternative embodiment of the capillary tube;

[0038]FIG. 8B is a greatly enlarged cross-sectional view taken alongline 8B-8B of FIG. 8A;

[0039]FIG. 9 is an enlarged cross-sectional view of yet anotheralternative embodiment of the capillary tube;

[0040]FIG. 10 is an enlarged sectional view through a portion of thecomponents shown in FIG. 3 to include means, e.g., a buffer piston atthe blood/transmission fluid interface to isolate the blood of the beingfrom the transmission fluid used by the system;

[0041]FIG. 11 is a block diagram of a portion of the system shown inFIG. 1, namely, the sensor means;

[0042]FIG. 12 is an enlarged cross-sectional view of the sensor meanstaken along line 12-12 of FIG. 2A;

[0043]FIG. 13 is an illustration of a calibration test rig for use withthe system of FIG. 1; and

[0044]FIG. 14 is a graph similar to FIG. 4 showing the head of thecolumn of fluid plotted versus time to show a thixotropic characteristicof the blood.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0045] Referring now in greater detail to the various figures of thedrawing, wherein like reference characters refer to like parts, there isshown in FIGS. 1A and 1B at 20 a liquid viscosity measuring systemconstructed in accordance with the present invention. The system 20 hasparticular utility for measuring in-vivo the viscosity of the blood of aliving being.

[0046] Although the apparatus 20 has many applications, the preferredembodiment of the apparatus 20 is used to measure the viscosity of theblood anywhere in a patient's vascular system, e.g., veins, arteries,pulmonary system, left atrium, left ventricle, etc.

[0047] It should be understood that blood is a non-Newtonian fluid. ANewtonian fluid may be defined as one in which the viscosity does notvary with the rate of shear within the non-turbulent flow range, whereasa non-Newtonian fluid, such as blood, exhibits a viscosity that isvariable with the rate of shear in the non-turbulent flow range. As aresult, when the viscosity of a non-Newtonian fluid is plotted as afunction of rate of shear, a curve is produced, instead of a straightline. Therefore, to obtain an accurate determination of blood viscosity,it is necessary to obtain a viscosity measurement over a range ofshears.

[0048] The concept of the present invention is to monitor, on asubstantially continuous basis, the rising head of an externally locatedcolumn of fluid coupled to a portion of the patient's body in which theblood flows, thus, effectively monitoring the patient's blood in-vivo.The data from this rising head is used to calculate the viscosity of theblood at a large multiplicity of points during the rise of the columnfor various different flow rates, thereby providing a viscosity of theblood over a range of shears. The monitoring of the rising column solvesthe problem of how to generate a range of shears necessary to obtain anaccurate measurement of the blood viscosity.

[0049] As shown in FIGS. 1A and 1B, the apparatus 20 basically comprisesa blood sampling means 22 and a calculation means 24 that are coupledtogether to provide the viscosity measurement. The blood sampling means22 comprises a catheter 26, which in a preferred embodiment comprises acapillary tube. The catheter 26 has an inside diameter D₁ and a length,L₁. The catheter 26 is introduced into the body 28 of the being(patient) to an internal situs 30 (e.g., a vein, artery, etc.) to enableblood 31 to flow into the catheter 26. Thus, the catheter 26 serves as ablood receiving means. The catheter 26 is connected via a hub 32 to aconduit means 34 having a inside diameter D₂. A first valve means 36(e.g., a 3-way valve) selectively couples an injector means 38 to theconduit means 34. The injector means 38 comprises a reservoir 40 forcontaining an indicator or transmission fluid 41 (e.g., a liquid such assaline solution, alcohol, or any sterile water-type liquid) which, wheninjected into the conduit means 34, forms a column of fluid 42 (to bediscussed later) that can be monitored (e.g., optically monitored-anoptimum dye can be used for coloring the transmission fluid formaximizing readability by an optical sensor). The other end of theconduit means 34 is coupled to a riser tube 44. The hollow interior ofthe riser tube 44 forms a lumen that permits the column of fluid 42level to be detected as a function of time. The riser tube 44 has aninside diameter of D₃. The upper end of the riser tube 44 comprises asecond valve means 46 (e.g., a 2-way valve) that vents the riser tube 44to atmosphere when the valve 46 is opened. The first valve means 36 andsecond valve means 46 preferably include hydrophobic vents (not shown)to eliminate blood spillage.

[0050] It should be understood that optimum selection of the tube sizesfor the capillary tube 26, the conduit means 34 and the riser tube 44minimizes the effects of viscosity and surface tension of thetransmission fluid 41. It should also be understood that it ispreferable to have the capillary tube 26 fully inserted into thevascular system, i.e., the capillary tube 26 is inserted such that acontinuation of the conduit means 34 of diameter D₂ is also disposed inthe vascular system.

[0051] The column of fluid 42 is monitored by monitoring means 48. Themonitoring means 48 comprises a sensor means 50 (e.g., a charge-coupleddevice, CCD, including associated electronics, FIG. 11 and an associatedpower supply 51) coupled to a microprocessor means 52 (e.g., a personalcomputer) which further comprises appropriate diagnostic software 54.The monitoring means 48 monitors the height of the column of fluid 42 asit rises throughout the length of the riser tube 44 during the test orrun to determine the patient's blood viscosity.

[0052] Peripheral indicator means 56, e.g., a visual display 58, acounter means 60, a printer 62, provides data and/or graphics pertainingto the viscosity/shear rate measurements. In addition, a modem 64 can beconnected to the monitoring means 48 to provide all pertinent data tosome remote location, e.g., via the Internet or World Wide Web 66.

[0053] In accordance with a preferred aspect of this invention, thevisual display 58 and/or printer 62 serve to present graphicalrepresentations of measured parameters such as viscosity vs. shear, orviscosity vs. height of column of fluid (“head”), or diagnoses. Thecounter means 60 is used to numerically display such items as viscosityat a particular shear and/or the head at which the velocity of thecolumn of fluid is zero, e.g., the thixotropic point (to be discussedlater). The viscosity/shear rate data can be stored in themicroprocessor means 52 and can be compared with databases 54 (onassociated CD-ROM, diskette or PC cards) to present possible diagnosesto the physician.

[0054]FIG. 2A depicts one portion of the implementation of the system20. As shown, the injector means 38, a portion of the conduit means 34,the first valve means 36, the riser 44, and the second valve means 46are mounted on a support plate 68 to form a tubing assembly 69. Thetubing assembly 69 is configured to be removably mounted inside ahousing 70 which contains the sensor means 50 and the power supply 51.The support plate 68 is mounted in the housing 70 with the appropriateconnections in order to position the riser tube 44 vertically anddirectly opposite the sensor means 50 for proper monitoring. Inaddition, during insertion of the tubing assembly 69, the appropriatevalve control connections 72 are made so that the first valve means 36and second valve means 46 can be properly controlled automatically insequence. Location pins 73 and location holes 75 are provided to ensurethat the support plate 68 is properly aligned, thereby disposing theriser tube 44 directly opposite the sensor means 50. The support plate68 comprises a transparent material that permits the sensor means 50 tooptically monitor the column of fluid 42. It should be understood thatthe injector means 38 is pre-charged with the transmission fluid 41which is held captive in the reservoir 40 by the 3-way valve 36. Onlywhen the valve 36 is properly oriented, does the transmission fluid 41flow out of the injector means 38 and into the conduit means 34.

[0055] Once the tubing assembly 69 is secured in the housing 70, a door74 can be releasably secured to create a sufficiently dark environmentto support proper column illumination 76 and level detection by thesensor means 50 during the run. Once a viscosity measurement procedureor run is completed, the tubing assembly 69 is removed, disconnectedfrom the capillary tube 26, and then discarded. To run another test, anew tubing assembly 69 is connected to the capillary tube 26 andre-installed into the housing 70.

[0056] It should be understood that it is within the broadest scope ofthis invention that the first 36 and second valve means 46 can becontrolled manually, i.e., proper operation of the apparatus 20 does notrequire automatic control of the first 36 and second valve means 46.

[0057] An exemplary test station is shown in FIG. 2B. It should beunderstood that although the apparatus 20 is shown with the capillary 26inserted into a patient's arm, the apparatus 20 is not limited in usewith that portion of the patient's body. Other station configurationscould be used where the capillary 26 is inserted into other portions ofthe patient's body for blood to flow into the capillary tube 26. Withthe test station shown in FIG. 2B, the patient 78 is seated with his/herarm disposed on a horizontal surface 80. The capillary 26 is insertedpercutaneously into the patient's arm until its distal end, andpreferably its entire length L₁, is within a desired vessel, e.g., avein. The conduit means 34 couples the capillary 26 to the housing 70.The housing 70 is releasably disposed on a fixed vertical surface 82.The vertical surface 82 comprises adjustment means 84 that permit theentire housing 70 to be manually displaced in a vertical direction andthen releasably secured at any desired vertical height. The importantpoint is that the operator can change the relative vertical position ofthe housing 70 with respect to the vertical position of the portion ofthe patient in which the capillary tube 26 has been inserted for reasonsto be understood later. The microprocessor means 52, visual display 58and printer 62 are also shown at the station.

[0058]FIG. 3 is a functional diagram of the apparatus 20. With respectto FIG. 3, the basic operation of the apparatus 20 is shown in FIG. 3.As blood 31 flows into and through the capillary tube 26 and into theconduit means 34, the blood 31 encounters the transmission fluid 41 anddisplaces the transmission fluid 41 up into the riser tube 44, therebyforming the column of fluid 42. The sensor means 50 (e.g., a CCD array)monitors the rise of the column of fluid 42 in real time by detectingthe interface between the top of the column of transmission fluid 42 andthe gas (e.g., air) in the riser tube above the fluid. This opticalinterface (e.g., meniscus) is readily detectable by the sensor means 50.Operation of the first valve means 36 and second valve means 46 arediscussed below.

[0059] If the following assumptions are made, in particular,

[0060] D₁ is much less than D₂; and

[0061] D₁ is much less than D₃

[0062] then it can be shown that the viscosity (η₁, (t)) and the shearrate ({dot over (γ)}1(t)) of the blood in the capillary tube 26 aregiven by:${\eta_{1}(t)} = {\left( \frac{\rho_{s}{gtD}_{1}^{4}}{32L_{1}D_{3}^{2}} \right) \cdot \frac{1}{\ln \left( \frac{h_{\infty}}{h_{\infty} - {h(t)}} \right)}}$${{{\overset{.}{Y}}_{1}(t)} = {\frac{8D_{3}^{2}}{D_{1}^{3}}\left( {{h_{\infty}\left( \frac{\rho_{s}g}{A} \right)}e^{- \frac{\rho_{s}{gt}}{A}}} \right)}},\quad {{{where}\quad A} = {32{\eta_{1}(t)}L_{1}\frac{D_{3}^{2}}{D_{1}^{4}}}}$

[0063] where η₁(t) represents the viscosity;

[0064] {dot over (γ)}₁(t) represents the shear rate;

[0065] ρ_(s) represents the density of the transmission or indicatorfluid;

[0066] g represents the gravitational constant;

[0067] t represents the time of measurement,

[0068] D₁ represents the inside diameter of the capillary tube;

[0069] L₁ represents the length of the capillary tube;

[0070] D₃ represents the inside diameter of the column of transmissionor indicator fluid;

[0071] h_(∞) represents the final height of the column of transmissionor indicator fluid; and

[0072] h(t) represents the instantaneous height of the column oftransmission or indicator fluid.

[0073] The viscosity, η₁(t), of the blood is thus graphicallyrepresented as shown in FIG. 4. To increase the range of shears, alonger capillary tube 26 can be used (i.e., increase L₁).

[0074] Operation of the apparatus 20 is depicted in FIGS. 5A-5H and isas follows:

[0075] The portion of the patient's vascular system (e.g., vein, artery,etc.) into which the capillary tube 26 is to be inserted is disposed onthe horizontal surface 80. This entry point on the patient becomes the“DATUM” reference and it represents a vertical height reference.

[0076] FIGS. 5A-5B: A guidewire 86 is introduced into the vascularsystem of the patient via a piercer 88. The piercer 88 is removed,leaving the guidewire 86 in place.

[0077] The following steps are preferably automated so that once thecapillary tube 26 is inserted in the patient, the operator need onlyactivate a switch (not shown) of a controller (also not shown) thatwould automatically carry out the following steps:

[0078]FIG. 5C: First valve means 36 is opened so that ports A and B arein communication while ports A to C and B to C are closed; the secondvalve means 46 is closed. The capillary 26 is then flushed.

[0079]FIG. 5D: First valve means 36 is totally closed and the capillary26 is threaded over the guidewire 86 and then disposed into thepatient's vascular system. The DATUM level is established for thecapillary tube 26 and the riser tube 44. A DATUM mark is made on thefixed vertical surface 82.

[0080]FIG. 5E: The guidewire 86 is removed and the DATUM level isestablished for the capillary tube 26 and the riser tube 44. A “0” markis created on the riser tube 44 that is aligned with the DATUM level.

[0081]FIG. 5F: First valve means 36 is moved to open communicationbetween ports A and C and second valve means 46 is moved to opencommunication between ports D and E. The operator then depresses theplunger 90 on the injection means 38 to fill the riser tube 44 withtransmission or indicator fluid up to the “0” or DATUM mark. Both thefirst valve means 36 and the second valve means 46 are then closed.

[0082]FIG. 5F: Permit blood pressure to pressurize the column of fluid42. The operator opens the first valve means 36 so that ports B and Care in communication, thereby permitting blood to flow (approximately0.5 cc of blood) into conduit means 34. The column of fluid 42 will risefrom the 0 mark to a new level. The operator then manually displaces thehousing 70 downward until the new level is aligned with the DATUM markon the fixed vertical surface 82. This action permits the determinationof blood's (e.g., the venous) static pressure using the closed-off risertube 44 as a “barometer.”

[0083]FIG. 5G: To avoid overflowing the riser tube 44 during the run, itis necessary to calculate the approximate final level or head, h_(∞), ofthe column of fluid 42 and to lower the housing 70 by that amount.Boyle's Law is used to estimate the likely rise h_(∞) of the column offluid 42 in step 5F. The housing 70 is then dropped by the amount h_(∞).The housing 70 is then secured at that height to prepare the sensormeans 50 to monitor the rise of the column of fluid 42. The second valvemeans 46 is then opened and the column of fluid 42 begins to rise.

[0084] If the test is to be run again, the tubing assembly 69 isdiscarded and a new tubing assembly 69 installed in the housing. If thetransmission fluid 41 in the injector means 38 is of a biocompatiblematerial, a portion of the transmission fluid 41 can be used to flushthe apparatus 20, all the way to the tip of the capillary tube 26, asshown in FIG. 5C.

[0085] Before a viscosity measuring run is made and as part of theautomated procedure discussed above, a current barometric pressurereading is obtained (e.g., from a barometer not shown, internal to thecalculation means 24) and is provided to the microprocessor means 52.Thus, the apparatus 20 calculates the proper viscosity/shear rate plotbased on the existing current atmospheric pressure. In addition, ventsmay be provided throughout the apparatus 20 to minimize the effect oncomputed viscosity accuracy.

[0086] It should be understood that the process described above couldalso be accomplished with the use of a hemostasis valve (e.g., a“Heparin Lock”) between the capillary tube 26 and the conduit means 34.This allows the capillary tube 26 to be left in place when a pluralityof runs are to be made. Furthermore, a hemostasis valve having a “Y”fitting could be disposed close to the point where the capillary tube 28enters the vessel in order to permit the passage of a the guide wire 86after the apparatus 20 is flushed without getting air bubbles.

[0087] The capillary tube 26 should constructed of, or coated with, amaterial or materials that prevent the blood 31 from adhering to thecapillary tube's internal walls, e.g., an anti-thrombogenic material,such as Heparin, and/or anti-thrombolytic coatings, e.g., phosphorylcholine, etc., can be used to minimize blood clotting. Phosphorylcholine compounds are available from Biocompatibles, Ltd., Uxbridge, UK.Such a construction or coatings facilitate the long-term placement ofthe capillary tube 26 within the vascular system of the patient.Furthermore, as shown most clearly in FIG. 6, the tip of the capillarytube 26 preferably comprises a plurality of ports 92. This ensures thatif the tip of the capillary tube 26 abuts any portion of the interior ofthe vessel wall once inserted into the patient's vascular system, bloodflow entry 94 into the capillary tube 26 will not be obstructed orimpeded.

[0088] An alternative embodiment of the capillary tube 26 is shown inFIG. 7 and includes an intravascular capillary with a controlled lumenor resistor for the viscometer function and with another for measuringpressure. For example, the capillary tube 126 comprises a first lumen 96for transmitting the blood 31 as discussed previously and comprises asecond lumen 98 that is coupled to a pressure transducer (not shown)that is coupled to the calculation means 24. Thus, the second lumen 98provides a continuous reference of the patient's blood pressure to thecalculation means 24. Unlike the process described earlier, whereby theoperator determines the patient's blood pressure before the test is run,using this second lumen 98, the calculation means 24 is provided with acontinuous blood pressure reference throughout the run. In somepatients, the actual blood pressure may change during the run. Suchblood pressure variations or pulsations need to be accounted for indetermining the proper viscosity/shear versus time curve. Having acontinuous blood pressure reference can thus be compensated for duringthe blood viscosity/shear determination.

[0089] Another alternative embodiment of the capillary tube 26 is shownin FIGS. 8A-8B and 9. This embodiment includes an intravascularcapillary with a controlled lumen or tube with alternative resistivemembers, such as a number of small capillary tubes in a bundle (FIGS.8A-8B). Alternatively, the tube is filled with very small spheres (FIG.9), or a sintered column (not shown). With respect to the embodiment asshown in FIGS. 8A-8B, the capillary tube 226 comprises a plurality ofsmall capillaries 100, each having different internal diameters (d₁, d₂,d₃, etc.). Use of the plurality of small capillaries not only permitsthe length L₁ to be smaller but also permits the attainment of verysmall shears. Where these diameters are less than the average diametersof a typical red blood cell, the system 20 can be used to determine theblood pressure at which blood flow starts. This action provides anindication of the deformability of the being's red blood cells sincethose cells will have to deform to pass through the small capillaries100.

[0090] In the alternative embodiment of the capillary tube shown in FIG.9, the capillary tube 326 includes very small spheres 102 within it tocreate interstices which are smaller than the average diameter of a redblood cell, so that such cells will have to deform to pass therethrough.

[0091] To eliminate or at least minimize the possiblemiscibility/contamination problem between the transmission fluid/bloodinterface in the conduit means 34, a buffer piston as shown in FIG. 10may be used. That piston can abe of any suitable construction, e.g., acarbon slug to isolate the blood 31 from the transmission fluid 41 attheir interface. In particular, the piston 104, having a specificgravity of approximately 1.0, transmits the motion or flow of the blood31 down the capillary tube to the transmission fluid 41 while isolatingor separating these two fluids from each other. Alternatively, althoughnot shown, a buffer fluid could be introduced at the interface betweenthe blood 31 and the transmission fluid 41 to reduce anymiscibility/contamination problems.

[0092]FIG. 11 is a block diagram of the sensor means 50, while FIG. 12shows its construction, i.e., a cross-sectional view of it taken alongline 12-12 of FIG. 2A but with the support plate 68 already secured tothe housing 70. Thus, as can be seen, an exemplary implementation of thesensor means 50 comprises a linear array of illuminators 76 (see FIGS.2A and 12), rod lenses 106, and sensor chips 108 mounted on a PCBsubstrate 110. One particularly useful commercial device incorporatingtheir components is the Model SV200A4 sold by Scan Vision, Inc. of SanJose, Calif. The sensor means 50 includes a glass cover 112 that abutsthe riser tube 44 when the support 68 is installed, as describedearlier. An integrated lens 114 may be disposed on the opposite side ofthe glass cover 112 to improve viewing by the rod lens 106.

[0093] In order for the system 20 to operate properly, it is necessaryfor the calculation means 24 to take into account the fluid resistanceof the tubing assembly 69 that is mounted in the housing 70. Toaccomplish that a test rig is utilized. FIG. 13 depicts an exemplarytest rig 116 for the tubing assembly 69 of the system 20. A bar code 118is provided on the support plate 68 (FIGS. 2A and 13) that contains acalibration factor for that particular tubing assembly 69. Thus, justbefore a viscosity run is made, an automatic scanner 119, coupled to thePC 52, scans the bar code 118 and loads the PC 52 with the particularcalibration factor.

[0094] To determine the calibration factor, the tubing assembly undercalibration, A₂, is coupled to the test rig 116, as shown in FIG. 13. Anair supply 120 delivers clean dry air at a predetermined pressure,P_(AS) (e.g., 100 psi) that can be regulated (via a regulator REG) downto 30 in H₂O. The air supply 120 delivers the flow through a calibratedorifice, A₁, having a known resistance. The input of the tubing assemblyunder test A₂ is coupled to the output of A₁ and the output of thetubing assembly under test A₂ is vented to atmosphere. When the airsupply 120 delivers the air flow, depending on the internal fluidresistance of the tubing assembly under test A₂, a pressure, P_(TA),appears at the input of the tubing assembly under test, A₂. A pair ofopen-ended manometers 122A and 122B are coupled to the input of A₁ andthe output of A₁, respectively, to monitor P_(AS) and P_(TA),respectively. The ratio P_(AS)/P_(TA) represents the calibration factor.This calibration factor is then encoded into the bar code 118. Thus,each time a tubing assembly 69 is mounted in the housing 70 and the barcode 118 read into the PC 52, the calculation means 24 can make aviscosity determination based on the specific fluid resistance of thatmounted tubing assembly 69.

[0095] In accordance with another aspect of the present invention and tominimize measurement errors, the system 20 includes the means forcontrolling the formation of a meniscus 124 (FIG. 3) at the top of thecolumn of transmission fluid 42. In particular, coatings for the risertube 44 can be introduced to control the surface tension precisely byproviding controlled surface energy, thus flattening the meniscus 124.This meniscus 124 can be further controlled by changing the molecularmake-up of the riser tube 44, the transmission fluid 41 being used andthe gas above the column of fluid 42. Furthermore, to make the surfaceenergy repeatable and predictable, the inner surfaces of riser tube 44maybe coated by vapor deposition with surfactants, e.g., silicone. Byincluding suitable surfactants, such as silicone, in the extrusions thesurfactants migrate to the surfaces in a predictable manner.

[0096] Another embodiment (not shown) of the apparatus 20 includes ariser tube 44 that is inclined to increase the sensitivity. Inparticular, if the riser tube 44 were angled away from a verticalorientation, for each millimeter rise in vertical height of the columnof fluid 42, there will be more than one millimeter of displacement ofthe column of fluid 42 in the riser tube 44.

[0097] In accordance with another aspect of the subject invention means124 (FIG. 2B can be provided to apply vibratory energy to the patient todetermine its effect on the patient's blood viscosity and the datadeveloped can then be used to provide customized vibratory therapy toprovide beneficial effects. In particular, that aspect of the inventionmakes use of a vibration source 124 that generates vibratory energywhose amplitude and frequency can be controlled by the operator. Thisvibratory energy is applied either before or during a viscositymeasuring run. Although the vibratory energy is shown in FIG. 2B asbeing applied to the patient's arm only, it is within the broadest scopeof the invention that the vibratory energy can be applied to all or onlya portion of the patient's body. The vibration may also be applied tothe column of fluid 42, and/or to the capillary tube 26, to obtain asmoother flow of fluid.

[0098] Another significant feature of the system 20 is its ability tomonitor the level of the column of fluid 42 at which the velocitybecomes zero, i.e., the thixotropic point of the blood flow. Thethixotropic point represents a shear stress being supported at zerovelocity, as graphically depicted in FIG. 14. Presentation of the shearor head at which flow restarts after a set time at zero motion providesan indication of the clotting characteristic of the patient.

[0099] It should be understood that the diagnostic software 54 allowsfor the dynamic effects of deceleration of the column of fluid 42 andfor the viscous effects of the various diameters of tubing as the blood31 and the transmission fluid 41 pass through the system 20.

[0100] It should be understood that another implementation of the system20 comprises a molded or etched channel system as a substitute for thetubing discussed above.

[0101] As mentioned earlier, the apparatus 20 has other applications,such as viscosity measurements of other flowable material, e.g., oils,paints and cosmetics.

[0102] Without further elaboration, the foregoing will so fullyillustrate our invention and others may, by applying current or futureknowledge, readily adapt the same for use under various conditions ofservice.

We claim:
 1. A system for effecting the measurement of the viscosity ofcirculating blood of a living being at plural shear rates, said systemcomprising a column having a liquid therein, a capillary tube, a sensingdevice and viscosity calculation means, said liquid in said columnhaving a top surface, said capillary tube being arranged to be insertedinto the vascular system of the being for providing blood from the beingto cause said liquid in said column to assume an initial level, saidcolumn being operative so that said liquid in said column is enabled todrop from said initial level to a lower level, said sensing device formonitoring the height of the liquid in the column at plural points alongthe column as said liquid drops in said column and for providingelectrical signals indicative thereof, said calculation means beingcoupled to said sensing device for receiving said electrical signals tocalculate the viscosity of the being's blood.
 2. The system of claim 1wherein said column is arranged so that the said liquid is enabled todrop therein under the force of gravity from said initial level.
 3. Thesystem of claim 1 wherein said sensor comprises a CCD device formonitoring the height of said liquid column.
 4. The system of claim 1wherein said liquid is not the blood of a being.
 5. The system of claim1 wherein said calculation means comprise a computer and associatedsoftware.
 6. The system of claim 1 wherein a fluid is located above saidtop surface of said liquid in said column, and wherein said top surfaceand said fluid define a machine determinable interface therebetween. 7.The system of claim 6 wherein said sensor comprises a CCD device fordetecting said interface.
 8. The system of claim 1 additionallycomprising a valve for selectively isolating said fluid in said columnfrom atmospheric pressure.
 9. The system of claim 8 wherein said valveis arranged to be in one state to isolate said fluid in said column fromthe ambient atmosphere when the blood of the being is being provided tocause said liquid in said column to assume said initial level, and to bein another state to enable said fluid to be at atmospheric pressure,whereupon said liquid begins to drop from said initial level.
 10. Asystem for effecting the measurement of the viscosity of the blood of aliving being at plural shear rates, said system comprising a columnhaving a liquid therein, said column being arranged to have blood fromthe being coupled thereto, said liquid in said column having a topsurface, said column being operative so that said liquid in said columnis enabled to drop from an initial level to a lower level, a sensingdevice for monitoring the height of the liquid in the column at pluralpoints along the column as said liquid drops in said column and forproviding electrical signals indicative thereof, and calculation meanscoupled to said sensing device for receiving said electrical signals tocalculate the viscosity of the being's blood.
 11. The system of claim 10wherein said column is arranged so that said liquid is enabled to droptherein under the force of gravity from said initial level.
 12. Thesystem of claim 10 wherein said sensor comprises a CCD device formonitoring the height of said liquid column.
 13. The system of claim 10wherein said liquid is not the blood of the being.
 14. The system ofclaim 10 wherein said calculation means comprises a computer andassociated software.
 15. The system of claim 10 wherein a fluid islocated above said top surface of said liquid in said column, andwherein said top surface and said fluid define a machine determinableinterface therebetween.
 16. The system of claim 15 wherein said sensorcomprises a CCD device for detecting said interface.
 17. The system ofclaim 10 additionally comprising a capillary tube arranged to beinserted into the vascular system of the being for providing blood fromthe being to cause said liquid in said column to assume said initiallevel.
 18. The system of claim 17 wherein said liquid is not the bloodof the being.
 19. The system of claim 10 additionally comprising a valvefor selectively isolating said fluid in said column from atmosphericpressure.
 20. The system of claim 19 wherein said valve is arranged tobe in one state to isolate said fluid in said column from the ambientatmosphere when the blood of the being is being provided to cause saidliquid in said column to assume said initial level, and to be in anotherstate to enable said fluid to be at atmospheric pressure, whereupon saidliquid begins to drop from said initial level.
 21. The system of claim17 additionally comprising a valve for selectively isolating said fluidin said column from atmospheric pressure.
 22. The system of claim 21wherein said valve is arranged to be in one state to isolate said fluidin said column from the ambient atmosphere when the blood of the beingis being provided to cause said liquid in said column to assume saidinitial level, and to be in another sate to enable said fluid to be atatmospheric pressure, whereupon said liquid begins to drop from saidinitial level.
 23. The system of claim 17 wherein said calculation meanscomprises a computer and associated software.